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This study confirms the observation that progesterone in viral and chemically induced carcinogenesis acts as a co-carcinogen. Intact C3HeB virgin female mice presumably free of the mammary tumor virus (MTV) were studied. In Group 1 progesterone 2.5 mg in .05 ml of peanut oil was injected sc 5 times a week for 19 weeks. Also 2 weeks after progesterone was started methylcholanthrene (MCA) .25 mg in .1 ml of Tween 60 was given by gastric lavage twice a week until mammary tumors were palpable. Group 2 was given the same MCA doses but only peanut oil sc. Group 3 received progesterone 5 times a week for 26 weeks and Tween only by gavage. Group 4 received the vehicles only. Group 5 was untreated. Groups 3 4 and 5 were completely free of mammary cancer. In weeks all mice developed mammary tumors and at 28 weeks all had died from their tumors. In another related experiment with C3H/He mice which were presumed to harbor the Bittner virus (MTV) Group 1 was treated with progesterone and MCA as before but the dose of MCA was increased to .5 mg twice weekly. Group 2 received .5 mg of MCA twice weekly but no progesterone only peanut oil. Group 3 received progesterone but no MCA only Tween. At the 41st week 8 tumor-free survivors of 25 mice of Group 3 were given progesterone repeatedly. Group 4 was untreated for 41 weeks and then given progesterone. Group 5 was given the vehicles only and Group 6 was untreated. In Group 6 3 and 33 mice developed mammary tumors after their 1st year of life. In Group 5 6 of 24 mice developed tumors. In Group 4 7 of 12 mice developed mammary tumors within 3 weeks after progesterone therapy was started. In Group 3 an early frequency of tumors had occurred but no increased incidence was noted after the later treatment. In Group 2 there was a greater tumor frequency an earlier appearance of tumors and a shorter life span than in Groups 3-6. In Group 1 high tumor incidence short life span and early appearance of tumors either noted. These experiments indicate that progesterone alone chemical carcinogen or with both agents acting together.